The pathophysiology and pathogenesis of bronchial asthma has been extensively studied in the past, and recent research directed at the underlying immunologic and neurogenic mechanisms have contributed significantly to our understanding of this complex disease. However, most investigators have been primarily interested in the mechanical effects of bronchoconstriction and its effect on gas exchange. Although the role of abnormal bronchial secretions in the pathogenesis of airway obstruction is well recognized by clinicians and pathologists, this aspect of bronchial asthma has been insufficiently examined. Similarly, the effects of the changes in airway function on pulmonary hemodynamics have not been systematically evaluated in the past. The major objective of this proposal is the study of mucociliary transport mechanisms and of the pulmonary circulation in animal models of bronchial asthma. Preliminary investigations have established that the conscious unsedated sheep is a promising animal model of experimental asthma, and the proposed experiments will be primarily conducted in sheep. For the study of the interrelationships among mucous transport, mucus rheology and respiratory mechanics in induced asthma, techniques previously developed in our laboratory such as radiographic estimation of tracheal mucous velocity and in vivo measurement of the viscoelastic properties of mucus will be used. The effects of abnormal airway mechanics and gas exchange on the lesser circulation will be studied in conscious animals. The possible pathogenetic role of known chemical mediators of the asthmatic response in the alterations of mucous transport and pulmonary hemodynamics as well as the modifying effect of pharmacologic agents will be evaluated. We expect the information derived from these studied to contribute to the understanding of two thus far only marginally explored aspects of bronchial asthma: mucociliary transport and pulmonary hemodynamics.